Tracking Antibiotic Effectiveness Worldwide 1999–2014 Using the Drug Resistance Index

Abstract

The effects of melatonin, amlodipine, diltiazem (L-type Ca 2+ channel blockers) and ω-conotoxin (N-type Ca 2+ channel blocker) on the glutamate-dependent excitatory response of striatal neurones to sensory-motor cortex stimulation was studied in a total of 111 neurones. Iontophoresis of melatonin produced a significant attenuation of the excitatory response in 85.2% of the neurones with a latency period of 2 min. Iontophoresis of either L- or N-type Ca 2+ channel blocker also produced a significant attenuation of the excitatory response in more than 50% of the recorded neurones without significant latency. The simultaneous iontophoresis of melatonin + amlodipine or melatonin + diltiazem did not increase the attenuation produced by melatonin alone. However, the attenuation of the excitatory response was significantly higher after ejecting melatonin + ω-conotoxin than after ejecting melatonin alone. The melatonin-Ca 2+ relationship was further supported by iontophoresis of the Ca 2+ ionophore A-23187, which suppressed the inhibitory effect of either melatonin or Ca 2+ antagonists. In addition, in synaptosomes prepared from rat striatum, melatonin produced a decrease in the Ca 2+ influx measured by Fura-2AM fluorescence. Binding experiments with [ 3 H]MK-801 in membrane preparations from rat striatum showed that melatonin did not compete with the MK-801 binding sites themselves although, in the presence of Mg 2+ , melatonin increased the affinity of MK-801. The results suggest that decreased Ca 2+ influx is involved in the inhibitory effects of melatonin on the glutamatergic activity of rat striatum.